Elevated resting energy expenditure (REE) may be a major determinant in the development of cancer cachexia. The aim of the study was to evaluate REE and body composition in cancer patients and find out the relationship between energy expenditure and substrate utilization. Measured resting energy expenditure (mREE), carbohydrate oxidation (C-O), and fat oxidation (F-O) were measured by indirect calorimetry in 714 cancer patients and 642 controls. Extracellular fluid (ECF), intracellular fluid (ICF), and total water (TW) were measured by bioelectrical impedance appliance; fat mass (FM), fat free mass (FFM), and body cell mass (BCM) were further determined. Compared with the controls, cancer patients showed no significant difference in mREE, but had higher mREE/FFM and mREE/pREE. 46.7% (n=333) of cancer patients were hypermetabolic, 43.5% (n=310) normometabolic, and 9.8% (n=71) hypometabolic; whereas 25.2% (n=162) of control subjects were hypermetabolic, 56.5% (n=363) normometabolic, and 18.3% (n=117) hypometabolic. Cancer patients showed an increase in F-O, ECF, TW/BW and ECF/BW; and a decrease in C-O, npRQ, ICF, ICF/BW. REE was correlated to substrate oxidation rate. Cancer patients exhibited an elevation in FM, FM/BW, FFM, and BCM, and a decrease in FFM/BW. 1. Cancer patients had elevated REE. Cancer type, pathological stage and duration of disease influenced REE. 2. Aberrations in substrate utilization may contribute to the elevated REE in cancer patients. 3. FM, FFM, and BCM diminished in cancer patients, which may be related to the elevated REE.